Ferrous fumarate 322mg / Folic acid 350microgram tablets

BACKGROUND: This review aims to assess the effect of oral administration of probiotics and/or prebiotics in children and women of reproductive age (WRA) to improve intestinal iron absorption, hemoglobin, and ferritin levels. METHODS: Randomized controlled trials from published literature on probiotics and or prebiotics for prevention or treatment of anemia as a supplement or fortification in children or WRA till Jan 31, 2023, were included. Studies on probiotics and prebiotics in patients with anemia due to other causes were excluded. Screening and data extraction was done using Distiller SR and meta-analysis was performed using Revman 5.4.1. RESULTS: A total of 1925 records were identified from Pubmed, Embase, and Cochrane, of which 29 were included in the systematic review (14 supplementation and 15 fortification studies; 15 studies in children and 14 studies in WRA). The major interventions included galacto-oligosaccharide, inulin, heat-killed H61, Lactobacillus plantarum 299v, Lactobacillus reuteri, Lactobacillus acidophilus. Meta-analysis of 5 studies in WRA showed that the use of prebiotics and/or probiotics with or without iron was associated with little or no effect on hemoglobin. However, there is low certainty of evidence that the intervention led to improvement in fractional absorption of iron as compared to placebo or iron [8 studies, n = 335, mean increase 0.74%, 95%CI-0.11-1.38, p = 0.02]. Meta-analysis of 6 studies in WRA using prebiotics and/or probiotics with or without iron led to a significant increase in ferritin levels in WRA (mean increase 2.45 ng/ml, 95% CI 0.61-4.3, p = 0.009, n = 320) [Moderate certainty of evidence]. In children, meta-analysis of up to 8 studies did not result in any significant change in hemoglobin, ferritin and fractional iron absorption [low or very low certainty of evidence]. CONCLUSION: There is some evidence to show that the use of prebiotics or probiotics (especially Lp299v and GOS) with or without oral iron can improve iron absorption in women and lead to improvement in ferritin levels in women. However, the current evidence does not conclusively show the benefit of these interventions in improving hemoglobin levels in women and children.

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Iron-Folic Acid (IFA) supplementation during pregnancy is widely recommended to prevent maternal anemia and improve birth outcomes. However, the optimal formulation, dose, and frequency of IFA supplementation remain uncertain. This systematic review and meta-analysis aimed to evaluate the effect of different IFA formulations, doses, and frequencies on pregnancy and neonatal outcomes compared to Multiple Micronutrients (MMN) among pregnant women. A comprehensive literature search was conducted across PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP databases to identify pertinent studies published up to December 31st, 2023. Outcome measures includes preterm birth (PTB), stillbirths, low birth weight (LBW), small for gestational age (SGA), miscarriage rate (MR), neonatal mortality, and perinatal mortality. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated, and the quality of evidence was assessed using GRADEpro. Among 20 studies comparing IFA to MMN, our analysis showed a significant increased risk with LBW (RR: 1.07, 95% CI: 1.01 to 1.13, p = 0.02, I2 = 24%) associated with IFA and MMN and elevated risk of stillbirth (RR: 1.08, 95% CI: 1.00 to 1.17, p = 0.05, I2 = 19%), SGA (RR: 1.03, 95% CI: 0.99 to 1.06) compared to IFA with MMN. However, non-significant risk of PTB (RR: 0.84, 95% CI: 0.38 to 1.84) and MR (RR: 1.04, 95% CI: 0.92 to 1.16, p = 0.54) was observed with IFA as compared to MMN. Neonatal mortality and perinatal mortality also did not significantly differ between the two groups. Certain formulations and doses showed trend of risk, particularly in relation to stillbirth and SGA. Our findings emphasize the importance of carefully considering the potential risks and benefits of IFA supplementation in pregnancy, and suggest the need for further research to elucidate the underlying mechanisms driving these associations and to optimize supplementation strategies for maternal and neonatal health.

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Nutritional deficiencies are prevalent in populations across the world. Fortification of staple foods has been used as an alternative to supplementation to address many deficiencies. One such staple is salt, which has long been fortified with iodine, but more recently with iron, folate, and other micronutrients. Our objective was to determine the effects of fortified salt on nutritional and health outcomes among children, adolescents, and adults. We conducted a systematic review of published and unpublished literature using a pre-defined search strategy. Abstracts and full texts were screened for randomized trials, quasi-randomized trials, and pre-post-designs of double or multiple fortified salt. We calculated the weighted pooled effect sizes for the effects of fortified salt on nutritional and health outcomes. Of the 395 studies identified, 33 (including 37 intervention-control comparisons) fit our inclusion criteria. Of these comparisons, 26 studied the effects of salt fortified with iron and iodine [double fortified salt (DFS)], 2 studied the effects of salt fortified with folic acid and iodine, 1 studied the effect of triple fortified salt, 1 studied the effect of quadruple fortified salt, and 7 studied the effects of multiple micronutrient fortified salt (MMFS; fortified with ≥5 nutrients). Pooled effect sizes indicated positive effects from all iron-containing fortified salt on hemoglobin concentration [standardized mean difference (95% confidence interval): DFS 0.36 (0.22, 0.50), n comparisons = 26; triple fortified salt 1.56 (1.42, 1.70), n comparisons = 1; quadruple fortified salt 0.33 (0.02, 0.63), n comparisons = 1; MMFS 0.23 (0.03, 0.43), n comparisons = 6]. DFS and MMFS reduced the odds of anemia and iron deficiency (ID) anemia. MMFS improved serum folate and reduced the odds of ID. Pooled effects on biomarkers of vitamin B12, vitamin A, and zinc status varied by type of salt, but were largely not significant. Fortification of salt with iodine and iron, with and without other nutrients, is effective in increasing hemoglobin and reducing the odds of anemia and ID in population-based studies.

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Innovative fortification solutions are needed to address micronutrient deficiencies, which remain highly prevalent among adult females in India. The objective of this trial was to evaluate the effects of quintuply-fortified salt (QFS) compared with iodized salt on the micronutrient status of nonpregnant females of reproductive age (NPFRA) in Punjab, India. We conducted a double-blind, randomized, controlled, community-based trial. A total of 998 NPFRA were randomly assigned to receive: 1 ) QFS with iron as encapsulated ferrous fumarate, zinc, vitamin B 12 , folic acid, and iodine (eFF-QFS); 2 ) QFS with the same micronutrients, but iron as encapsulated ferric pyrophosphate plus ethylenediaminetetraacetic acid (eFePP-QFS); or 3 ) iodized salt. Biomarkers of micronutrient status were assessed at enrollment, 6 mo and 12 mo. At enrollment, the prevalence of anemia, iron deficiency, hypozincemia, vitamin B 12 insufficiency, and folate insufficiency among trial participants was 47.9%, 59.7%, 35.5%, 61.5%, and 69.7%, respectively. Mean household salt disappearance, measured at monthly home visits, was 6.0 g/adult female equivalent/day [95% confidence interval (CI): 5.9, 6.1] and did not vary across groups or time. At 6 mo, the odds of vitamin B 12 insufficiency, folate insufficiency, and hypozincemia were, respectively, 80% [odds ratio (OR): 0.20; 95% CI: 0.13, 0.31], 86% (OR: 0.14; 95% CI: 0.09, 0.21), and 38% (OR: 0.62; 95% CI: 0.41, 0.93) lower in the eFF-QFS compared with the iodized salt group. Effects on vitamin B 12 and folate status were sustained at 12 mo, and were comparable in the eFePP-QFS compared with the iodized salt group. There was a small, marginally significant, reduction in iron deficiency in the eFF-QFS compared with the iodized salt group at 6 (OR: 0.64; 95% CI: 0.42, 0.98; P = 0.08) and 12 mo (OR: 0.58; 95% CI: 0.35, 0.95; P = 0.06), but not in the eFePP-QFS compared with the iodized salt group. There were no groupwise differences in anemia at either time point. Multiple micronutrient salt fortification may be an effective strategy to improve micronutrient status, especially vitamin B 12 and folate, among NPFRA at high risk of deficiency. This study was registered at clinicaltrials.gov , with NCT05166980 and at Clinical Trials Registry-India with CTRI/2022/02/040333.

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BACKGROUND: Micronutrient deficiencies remain prevalent among preschool-aged children (PSC) in India. Quintuply-fortified salt (QFS) is one of many potential interventions to improve micronutrient intake and status at the population level. OBJECTIVES: To determine the effect of QFS compared with iodized salt (IS) for 12 mo on the micronutrient status of PSC. METHODS: This was a substudy of a double-blinded, household-randomized, controlled, community-based trial involving nonpregnant females of reproductive age whose households were randomly assigned to receive: 1) QFS with zinc, vitamin B-12, folic acid, iodine, and iron as encapsulated ferrous fumarate (eFF-QFS); 2) QFS with the same micronutrients, but iron as encapsulated ferric pyrophosphate plus ethylenediaminetetraacetic acid (eFePP-QFS); or 3) IS. The micronutrient status of 470 PSC (aged 12-59 mo) residing in these households was assessed at enrollment, 6 mo, and 12 mo. Continuous outcomes were analyzed with linear regression and reported as means or geometric mean ratios, and binary outcomes were analyzed with logistic regression and reported as odds ratios. RESULTS: At baseline, the prevalence of anemia, iron deficiency anemia, hypozincemia, vitamin B-12 insufficiency, and folate deficiency was 35%, 30%, 14%, 17%, and 5.5%, respectively. Effects of QFS at 6 and 12 mo were greatest for vitamin B-12 and folate. At 12 mo, the eFePP-QFS group had higher serum vitamin B-12 [geometric mean ratio (GMR) = 1.16, 95% confidence interval (CI) = 1.03, 1.30], serum folate (GMR = 1.29, 95% CI = 1.09, 1.53), and red blood cell folate (GMR = 1.21, 95% CI = 1.05, 1.39) concentrations compared with the IS group. Effects were similar among the 2 QFS groups. There were no significant differences in serum zinc, ferritin, hemoglobin, or urinary iodine between groups at 6 and 12 mo. CONCLUSIONS: Preschool children consuming QFS for 12 mo demonstrated greater improvements in vitamin B-12 and folate status compared with children consuming IS. QFS may be a useful vehicle to address micronutrient deficiencies, especially vitamin B-12 and folate, in this population.

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<h2>Abstract</h2><h3>Background</h3> Young children in India often face multiple micronutrient deficiencies, yet interventions such as micronutrient powders (MNPs) have raised concerns about potential adverse effects on the gut microbiome. Large‐scale food fortification (LSFF) is an effective strategy to improve micronutrient intake, however, its impact on the gut microbiome of children remains unclear. <h3>Objective</h3> To determine whether intake of quintuply fortified salt (QFS) for 12 months adversely affects gut microbiome composition in children aged 1-5 years. <h3>Methods</h3> In a double‐blind, randomized, controlled trial in Punjab, India, children received: 1) QFS with iron as encapsulated ferrous fumarate, zinc, vitamin B12, folic acid, and iodine (eFF‐QFS); 2) QFS with the same micronutrients, but iron as encapsulated ferric pyrophosphate plus EDTA (eFePP‐QFS); or 3) standard iodized salt for 12 months. Stool samples were collected from 125 children (eFF-QFS, n=43; eFePP-QFS, n=45; iodized salt, n=37) at baseline and 12 months and analyzed via 16S rRNA gene sequencing. Changes in alpha diversity (Shannon, ACE index) between groups were assessed with linear mixed models, beta diversity (Bray-Curtis dissimilarity) with linear regression and PERMANOVA, and relative abundance of <i>Enterobacteriaceae, Lactobacillus, Bifidobacterium, Bacteroides, Prevotella or Escherichia-Shigella</i> with zero‐inflated negative binomial mixed models. <h3>Results</h3> Average discretionary salt utilization was estimated to be 3.5 g/child equivalent/day across groups. ACE index was higher in the iodized salt arm versus eFePP-QFS, but similar to eFF-QFS. PERMANOVA revealed no overall group differences; however, pairwise Bray-Curtis distances from baseline were modestly greater in eFF-QFS versus the other groups. No significant changes in relative abundance were identified. <h3>Conclusions</h3> After 12 months, QFS resulted no major changes in abundance of key taxa and minimal, inconsistent shifts in certain diversity metrics and relative to the iodized salt control, suggesting no adverse effects on microbiome composition among young children in this setting. Additional studies in settings with improved iron status are needed. <h3>Clinical Trial Registration</h3> ClinicalTrials.gov number, NCT05166980; Clinical Trials Registry- India, CTRI/2022/02/040333

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BACKGROUND: Iron and folic acid supplementation have been recommended in pregnancy for anaemia prevention, and may improve other maternal, pregnancy, and infant outcomes. OBJECTIVES: To examine the effects of daily oral iron supplementation during pregnancy, either alone or in combination with folic acid or with other vitamins and minerals, as an intervention in antenatal care. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Registry on 18 January 2024 (including CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, conference proceedings), and searched reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials that evaluated the effects of oral supplementation with daily iron, iron + folic acid, or iron + other vitamins and minerals during pregnancy were included. DATA COLLECTION AND ANALYSIS: Review authors independently assessed trial eligibility, ascertained trustworthiness based on pre-defined criteria, assessed risk of bias, extracted data, and conducted checks for accuracy. We used the GRADE approach to assess the certainty of the evidence for primary outcomes. We anticipated high heterogeneity amongst trials; we pooled trial results using a random-effects model (average treatment effect). MAIN RESULTS: We included 57 trials involving 48,971 women. A total of 40 trials compared the effects of daily oral supplements with iron to placebo or no iron; eight trials evaluated the effects of iron + folic acid compared to placebo or no iron + folic acid. Iron supplementation compared to placebo or no iron Maternal outcomes: Iron supplementation during pregnancy may reduce maternal anaemia (4.0% versus 7.4%; risk ratio (RR) 0.30, 95% confidence interval (CI) 0.20 to 0.47; 14 trials, 13,543 women; low-certainty evidence) and iron deficiency at term (44.0% versus 66.0%; RR 0.51, 95% CI 0.38 to 0.68; 8 trials, 2873 women; low-certainty evidence), and probably reduces maternal iron-deficiency anaemia at term (5.0% versus 18.4%; RR 0.41, 95% CI 0.26 to 0.63; 7 trials, 2704 women; moderate-certainty evidence), compared to placebo or no iron supplementation. There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence). The evidence is very uncertain for adverse effects (21.6% versus 18.0%; RR 1.29, 95% CI 0.83 to 2.02; 12 trials, 2423 women; very low-certainty evidence) and severe anaemia (Hb < 70 g/L) in the second/third trimester (< 1% versus 3.6%; RR 0.22, 95% CI 0.01 to 3.20; 8 trials, 1398 women; very low-certainty evidence). No trials reported clinical malaria or infection during pregnancy. Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation. However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence). There is probably little to no difference in preterm birth (7.6% versus 8.2%; RR 0.93, 95% CI 0.84 to 1.02; 11 trials, 18,827 infants; moderate-certainty evidence) and there may be little to no difference in neonatal death (1.4% versus 1.5%, RR 0.98, 95% CI 0.77 to 1.24; 4 trials, 17,243 infants; low-certainty evidence) or congenital anomalies, including neural tube defects (41 versus 48 events; RR 0.88, 95% CI 0.58 to 1.33; 4 trials, 14,377 infants; low-certainty evidence). Iron + folic supplementation compared to placebo or no iron + folic acid Maternal outcomes: Daily oral supplementation with iron + folic acid probably reduces maternal anaemia at term (12.1% versus 25.5%; RR 0.44, 95% CI 0.30 to 0.64; 4 trials, 1962 women; moderate-certainty evidence), and may reduce maternal iron deficiency at term (3.6% versus 15%; RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low-certainty evidence), compared to placebo or no iron + folic acid. The evidence is very uncertain about the effects of iron + folic acid on maternal iron-deficiency anaemia (10.8% versus 25%; RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; very low-certainty evidence), or maternal deaths (no events; 1 trial; very low-certainty evidence). The evidence is uncertain for adverse effects (21.0% versus 0.0%; RR 44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; low-certainty evidence), and the evidence is very uncertain for severe anaemia in the second or third trimester (< 1% versus 5.6%; RR 0.12, 95% CI 0.02 to 0.63; 4 trials, 506 women; very low-certainty evidence), compared to placebo or no iron + folic acid. Infant outcomes: There may be little to no difference in infant low birthweight (33.4% versus 40.2%; RR 1.07, 95% CI 0.31 to 3.74; 2 trials, 1311 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. Infants born to women who received iron + folic acid during pregnancy probably had higher birthweight (MD 57.73 g, 95% CI 7.66 to 107.79; 2 trials, 1365 infants; moderate-certainty evidence), compared to placebo or no iron + folic acid. There may be little to no difference in other infant outcomes, including preterm birth (19.4% versus 19.2%; RR 1.55, 95% CI 0.40 to 6.00; 3 trials, 1497 infants; low-certainty evidence), neonatal death (3.4% versus 4.2%; RR 0.81, 95% CI 0.51 to 1.30; 1 trial, 1793 infants; low-certainty evidence), or congenital anomalies (1.7% versus 2.4; RR 0.70, 95% CI 0.35 to 1.40; 1 trial, 1652 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. A total of 19 trials were conducted in malaria-endemic countries, or in settings with some malaria risk. No studies reported maternal clinical malaria; one study reported data on placental malaria. AUTHORS' CONCLUSIONS: Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term. For other maternal and infant outcomes, there was little to no difference between groups or the evidence was uncertain. Future research is needed to examine the effects of iron supplementation on other maternal and infant health outcomes, including infant iron status, growth, and development.

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Pyrite, the most abundant iron sulfide mineral in the Earth's crust, has traditionally been considered as a sink for iron and sulfur in the absence of oxygen. Recent research, however, has shown that anaerobic methanogenic archaea can reductively dissolve pyrite and assimilate its products as sources of iron and sulfur. This study explores whether other anaerobic bacteria, including fermentative, nitrate-, iron oxide-, fumarate-, and sulfate-respiring bacteria, can also reduce pyrite and use its dissolution products as sources of iron and sulfur. Results indicate that heterotrophic bacteria respiring fumarate or sulfate, or fermenting organic carbon, can reduce pyrite and assimilate released iron and sulfur. In contrast, nitrate- or iron oxide-respiring cells did not reduce pyrite, suggesting that microbial pyrite reduction is metabolism-specific. All strains capable of reducing pyrite could also use mackinawite as an iron and sulfur source. With the exception of fermentative Bacteroides, strains did not require direct contact with pyrite to reduce the mineral, indicating extracellular electron transfer via electron shuttles. These findings expand the known diversity of microbial groups capable of pyrite reduction and highlight the mineral's lability in various anaerobic environments, with potential implications for the biogeochemical cycles of iron, sulfur, carbon, and oxygen.

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